HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to POTELIGEO Prescribing Information for complete information.
Kyowa Kirin Inc.
Approval date: August 8, 2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
POTELIGEO is used to treat adults with mycosis fungoides (MF) or Sézary syndrome (SS) who have received at least one prior systemic (such as injections or pills) treatment for their disease but the treatment did not work or the disease has come back.
MF and SS are rare types of cancer called cutaneous T-cell lymphoma which form in the lymph system and affect the skin.
How is this drug used?
POTELIGEO is given by a healthcare provider directly into the bloodstream through a needle in the vein. This is known as an intravenous, or IV infusion. It takes about one hour to receive a POTELIGEO infusion.
POTELIDEO is given on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle.
What are the benefits of this drug?
In the trial, patients who received POTELIGEO experienced longer period of time a patient stays alive without the cancer growing (called progression-free survival) in comparison to patients who received vorinostat (a type of chemotherapy) . For patients treated with POTELIGEO it took about 7.6 months before disease progression and for patients treated with vorinostat about 3.1 months.
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results based on the investigator-assessed progression-free survival (PFS), which was defined as the time from the date of randomization until documented progression of disease or death. Other efficacy measures included overall response rate (ORR) based on global composite response criteria that combine measures from each disease compartment (skin, blood, lymph nodes and viscera).
Table 2: Efficacy of Randomized Treatment
|Outcome per Investigator||POTELIGEO|
|Number of events, n||110||131|
|Median PFS (95% CI) (months) a||7.6 (5.6, 10.2)||3.1 (2.8, 4.0)|
|Hazard ratio (95% CI)|
Log rank p-value
|0.53 (0.41, 0.69)|
|Overall response rate |
(confirmed CR + PR), n (%) b, c
|52 (28)||9 (5)|
|95% CI||(22, 35)||(2, 9)|
|Duration of overall response (months)|
|Median (95% CI) a||13.9 (9.3, 18.9)||9.0 (4.6, NE)|
|Confirmed best overall response b|
|CR, n (%)||4 (2)||0 (0)|
|95% CI||(1, 5)||(0, 2)|
|PR, n (%)||47 (25)||9 (5)|
|95% CI||(20, 33)||(2, 9)|
|Response by compartment (confirmed CR + PR) c|
|Response rate, n (%)||83 (67)||23 (18)|
|95% CI||(58, 75)||(12, 26)|
|Response rate, n (%)||78 (42)||29 (16)|
|95% CI||(35, 49)||(11, 22)|
|Response rate, n (%)||21 (15)||5 (4)|
|95% CI||(10, 23)||(1, 9)|
|Response rate, n (%)||0 (0)||0 (0)|
|95% CI||(0, 46)||(0, 60)|
a Kaplan-Meier estimate.
b Based on Global Composite Response score.
c Responses in blood and skin must have persisted for at least 4 weeks to be considered confirmed and were evaluated every 4 weeks for the first year. Responses in lymph nodes, visceral disease and overall were evaluated every 8 weeks for the first year.
d From Cochran-Mantel-Haenszel test adjusted for disease type, stage, and region.
CI=confidence interval; CR=complete response; NE=not estimable; PR=partial response
POTELIGEO Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: POTELIGEO worked similarly in men and women.
- Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
- Age: POTELIGEO worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The table below summarizes efficacy results by demographic subgroups based on PFS.
Table 3. Subgroup Efficacy Analyses
|Sex (n/N1, %)|
|Men||63/109 (57.8)||82/107 (76.6)||0.46 (0.33,0.65)|
|Women||47/77 (61)||49/79 (62)||0.62 (0.41, 0.94)|
|Race (n/N1, %)|
|White||74/125 (59.2)||95/135 (70.4)||0.51 (0.37, 0.70)|
|Black or African American||15/24 (62.5)||8/13 (61.5)||0.79 (0.32, 1.92)|
|Other||21/37 (56.8)||28/38 (73.7)||0.50 (0.28, 0.91)|
|Age Group (n/N1, %)|
|65>||62/99 (62.6)||63/89 (70.8)||0.59 (0.41, 0.85)|
|≥65 years||48/87 (55.2)||68/97 (70.1)||0.46 (0.31, 0.68)|
Adapted from FDA Review
What are the possible side effects?
POTELIGEO may cause serious side effects including life threatening rash, infusion reactions, infections, and worsening of autoimmune diseases and complications of stem cell transplantation.
The most common side effects of POTELIGEO are rash, infusion related reactions, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection.
What are the possible side effects (results of trials used to assess safety)?
The table below summarizes common adverse reactions that occur during the clinical trial.
Table 4. Common Adverse Reactions (≥10%) with ≥2% Higher Incidence in the POTELIGEO Arm
by Body System a, b
|Skin and Subcutaneous Tissue Disorders|
|Rash, Including Drug Eruption||35||5||11||2|
|Infusion Related Reaction||33||2||0||0|
|Upper Respiratory Tract Infection||22||0||16||1|
|Musculoskeletal and Connective Tissue Disorders|
a Adverse reactions include groupings of individual preferred terms.
b Includes adverse reactions reported up to 90 days after randomized treatment.
Rash/Drug Eruption includes: dermatitis (allergic, atopic, bullous, contact, exfoliative, infected), drug eruption, palmoplantar keratoderma, rash (generalized, macular, maculopapular, papular, pruritic, pustular), skin reaction, toxic skin eruption
Upper Respiratory Tract Infection includes: laryngitis viral, nasopharyngitis, pharyngitis, rhinitis, sinusitis, upper respiratory tract infection, viral upper respiratory tract infection
Skin Infection includes: cellulitis, dermatitis infected, erysipelas, impetigo, infected skin ulcer, periorbital cellulitis, skin bacterial infection, skin infection, staphylococcal skin infection
Musculoskeletal Pain includes: back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, pain in extremity
Mucositis includes: aphthous stomatitis, mouth ulceration, mucosal inflammation, oral discomfort, oral pain, oropharyngeal pain, stomatitis
POTELIGEO Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The occurrence of side effects was similar in men and women.
- Race: Most of the patients were White. Differences in the occurrence of side effects among races could not be determined because of the small number of patients in other races.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
Tables below summarize treatment emergent and serious adverse events that occurred during the clinical trials by sex and age subgroup.
Table 5. Subgroup Analyses of Treatment Emergent Adverse Events (TEAE)
|Patients with any TEAE, n/N (%)||179/184 (97.3)||185/186 (99.5)|
|Sex, n/N1 (%)|
|Men||63/107 (58.9)||82/107 (76.6)|
|Women||47/77 (61)||49/79 (62)|
|Age Group, n/N1 (%)|
|65>||62/99 (62.6)||63/89 (70.8)|
|≥65 years||48/85 (56.5)||68/97 (70.1)|
Clinical Trial Report
Table 6. Subgroup Analyses of Serious Adverse Events (SAE)
|Patients with any SAE, n/N (%)||69/184 (37.5)||46/186 (24.7)|
|Sex, n/N1, (%)|
|Men||38/107 (36)||21/107 (20)|
|Women||28/77 (36)||24/79 (30)|
|Age Group, n/N1, (%)|
|65>||34/99 (34)||19/89 (21)|
|≥65 years||32/85 (38)||26/97 (27)|
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved POTELIGEO based on evidence from one clinical trial (NCT01728805) which enrolled 372 patients with MF or SS who had received at least one prior therapy for the disease.
The trial was conducted in United States, Europe, Japan and Australia.
Figure 1 summarizes how many men and women were in the clinical trial.
Figure 1. Baseline Demographics by Sex
Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trial.
Figure 2. Baseline Demographics by Race
Table 1. Baseline Demographics by Race
|Race||Number of Patients||Percentage|
|Black or African American||37||10|
* Data on race and/or ethnicity were not collected in some European countries because of local regulations.
Figure 3 summarizes how many patients of certain age were enrolled in the clinical trial.
Figure 3. Baseline Demographics by Age
Who participated in the trials?
The table below summarizes demographics of all patients enrolled in the clinical trial.
Table 7. Baseline Demographics of Patients Enrolled in the Clinical Trial
(N = 372)
|Sex (n, %)|
|Men||109 (58.6)||107 (57.5)||216 (58.1)|
|Women||77 (41.4)||79 (42.5)||156 (41.9)|
|Race (n, %)|
|White||125 (67.2)||135 (72.6)||260 (69.9)|
|Black or African American||24 (12.9)||13 (7.0)||37 (9.9)|
|Asian||12 (6.5)||7 (3.8)||19 (5.1)|
|American Indian or Alaskan Native||0||1 (0.5)||1 (0.3)|
|Native Hawaiian or Other Pacific Islander||1 (0.5)||0||1 (0.3)|
|Other||0||5 (2.7)||5 (1.3)|
|Unknown*||24 (12.9)||25 (13.4)||49 (13.2)|
|Mean (SD)||62.8 (13.34)||63.3 (12.58)||63 (12.95)|
|Median (min, max)||63.5 (25, 101)||65 (25, 89)||64 (25,101)|
|Age Group (n, %)|
|18 – 64 years||99 (53.2)||89 (47.8)||188 (50.5)|
|≥ 65 years||87 (46.8)||97 (52.2)||184 (49.5)|
|Ethnicity (n, %)|
|Hispanic or Latino||6 (3.2)||9 (4.8)||15 (4.0)|
|Not Hispanic or Latino||155 (83.3)||152 (81.7)||307 (82.5)|
|Unknown*||23 (12.4)||25 (13.4)||48 (12.9)|
|Missing||2 (1.1)||0||2 (0.5)|
|Region (n, %)|
|US||98 (52.7)||103 (55.4)||201 (54.0)|
|Europe||70 (37.6)||70 (37.6)||140 (37.6)|
|Japan||9 (4.8)||6 (3.2)||15 (4.0)|
|Rest of World||9 (4.8)||7 (3.8)||16 (4.3)|
*Data on race and/or ethnicity were not collected in some European countries because of local regulations.
Adapted from FDA Review
How were the trials designed?
There was one trial that evaluated the benefit and side effects of POTELIGEO in patients with MF or SS who had received at least one prior systemic therapy.
Half of the patients received POTELIGEO infusion and the other half vorinostat capsules (a previously approved drug to treat skin lymphoma). POTELIGLEO was given once a day on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle and vorinostat capsules daily for 28-day cycles. Both, patients and health care providers knew which treatment was given.
Treatment continued until disease progression or unacceptable side effects.
The benefit of POTELIGEO was evaluated by measuring the length of time during which patients stay alive without the cancer growing (progression-free survival or PFS) and comparing it to PFS in patients who took vorinostat.
How were the trials designed?
The safety and efficacy of POTELIGEO were established in one, actively controlled (vorinostat), multicenter, open-label trial that enrolled adult patients with relapsed or refractory mycosis fungoides or Sézary syndrome who had received at least one prior therapy.
Patients received POTELIGEO as 1 mg/kg administered intravenously over at least 60 minutes on days 1, 8, 15, and 22 of the first 28-day cycle and on days 1 and 15 of each subsequent cycle. Vorinostat was dosed at 400 mg orally once daily, continuously for 28-day cycles. Both treatments were given until disease progression or unacceptable toxicity. Vorinostat-treated patients with disease progression or unacceptable toxicities were permitted to cross over to POTELIGEO. The median duration of POGLITEO treatment was 5.6 months (range: 1>1>
The efficacy was established based on investigator-assessed progression-free survival (PFS), which was defined as the time from the date of randomization until documented progression of disease or death. Other efficacy measures included overall response rate (ORR) based on global composite response criteria that combine measures from each disease compartment (skin, blood, lymph nodes and viscera). Responses required confirmation at two successive disease assessments, which included the modified Severity Weighted Assessment Tool, skin photographs, central flow cytometry, and computed tomography.
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.